Organophosphate ester derivatives of heterocyclic compounds and process

ABSTRACT

An organophosphate ester having the formula   WHEREIN A represents a divalent radical selected from the group consisting of alkylene having three to five carbon atoms, aza substitued alkylene having three to five carbon atoms in the chain and thia substituted alkylene having three to five carbon atoms in the chain, Y&#39;&#39; represents a member selected from the group consisting of hydrogen, alkyl having one to six carbon atoms, cyano, halo and alkylthio having one to six carbon atoms, X represents a member selected from the group consisting of sulfur and oxygen, R1&#39;&#39;&#39;&#39; represents an alkyl having one to four carbon atoms, R2&#39;&#39;&#39;&#39; represents a member selected from the group consisting of alkyl having one to four carbon atoms, alkoxy having one to four carbon atoms, alkoxyalkoxy having one to four carbon atoms in each alk, and   WHERE R1&#39;&#39; and R2&#39;&#39; are members selected from the group consisting of hydrogen and alkyl having one to three carbon atoms; as well as the process of producing said organophosphate esters. The compounds have insecticidal and acaricidal properties.

United States Patent [1 1 Perronnet et al.

[ Dec. 31, 1974 ORGANOPHOSPHATE ESTER DERIVATIVES OF I-IETEROCYCLICCOMPOUNDS AND PROCESS [75] Inventors: Jacques Perronnet, Paris; AndrePoittevin, Vaires-sur-Marne, both of France [73] Assignee: RousselUclaf, Paris, France [22] Filed: Sept. 12, 1972 [21] Appl. No.:'288,393

[30] Foreign Application Priority Data Sept. 16, l97l France 71.33434[52] US. Cl. 260/243 R, 260/25 A, 260/25 P,

260/256,4 E, 260/256.4 F, 260/256.5 R, 424/200 [51] Int. Cl C07d 51/46[58] Field of Search 260/251 A, 251 P, 256.4 E, 260/243 R, 256.5 R

[56] References Cited UNITED STATES PATENTS 9/ 1 968' Schicke 260/256.4

Primary E.\'aminerRaymond V. Rush Attorney, Agent, or Firm--Hammond &Littell substituted wherein "A represents a divalent radical selectedfrom the group consisting of alkylene having three to five carbon atoms,aza substitued alkylene having atoms, alkoxy having one to four carbonatoms, alkoxyalkoxy having'one to four carbon atoms in each alk, and

where R, and R are members selected from the group consisting ofhydrogen and alkyl having one to three carbon atoms; as well as theprocess of producing said organophosphate esters. The compounds haveinsecticidal and acaricidal properties 4 Claims, N0 DrawingsORGANOPIIOSPIIATE ESTER DERIVATIVES OF IIETEROCYCLIC COMPOUNDS ANDPROCESS OBJECTS OF THE INVENTION T N A wherein A represents a divalentradical selected from the group consisting of alkylene having three tofive carbon atoms, aza substituted alkylene having three to five carbonatoms in the chain and thia substituted alkylene having three to fivecarbon atoms in the chain,

Y represents a member selected from the group consisting of hydrogen,alkyl having one to six carbon atom, cyano, halo and alkylthio havingone to six carbon atoms,

X represents a member selected from the group consisting of sulfur andoxygen,

R," represents an alkyl having one to four carbon atoms,

R represents a member selected from the group consisting of alkyl havingone to four carbon atoms, alkoxy having one to four carbon atoms, al-

koxyalkoxy havingl to 4 carbon atoms in each alk, and

where R, and R are members selected from the group consisting ofhydrogen and alkyl having one to wherein A represents a divalent radicalselected from the group consisting of alkylene having three to fivecarbon atoms, aza substituted alkylene having three to five carbon atomsin the chain and thia substituted al kylene having three to five carbonatoms in the chain and Y represents a member selected from the groupconsiting of hydrogen, alkyl having from one to six carbon atoms, cyano,halo and alkylthio having from one to six carbon atoms. with ahalophosphate having the formula wherein Hal represents a memberselected from the group consisting of chloro and bromo, X represents amember selected from the group consisting of sulfur and oxygen, Rrepresents an alkyl having one to four carbon atoms and R represents amember selected from the group consisting of alkyl having one to fourcarbon atoms, alkoxy having one to four carbon atoms, alkoxyalkoxyhaving one to four carbon atoms in eac alk, and

where R, and R are members selected from the group consisting ofhydrogen and alkyl having one to three carbon atoms, and recovering saidorganophosphate ester.

A further object ofthe present invention is the development ofinsecticidal and/or acaricidal compositions containing from 10 percentto percent of the above organophosphate esters and the remainder inertexcipients.

A yet further object of the present invention is the development ofamethod for combatting insects and/or acarids which comprises contacting'them with the above organophosphate esters.

These and other objects of the invention will become more apparent asthe description thereof proceeds.

DESCRIPTION OF THE INVENTION The above objects have been achieved by thediscovery of novel insecticidal and/or acaricidal organophosphate esterderivatives of the general formula I in which A represents an alkylenechain having from three to five carbon atoms, possibly interrupted by abeteroatom chosen from sulfur and nitrogen, and more particularly Arepresents a divalent radical selected from the group consisting ofalkylene having three to five carbon atoms, aza substituted alkylenehaving three to five carbon atoms in the chain and thia substitutedalkylene having three to five carbon atoms in the chain;

Y represents hydrogen, alkyl having one to six carbon atoms, linear orbranched, cyano, halogen or alkylthio having one to six carbon atoms,and more praticularly Y represents a member selected from the groupconsisting of hydrogen, alkyl having from one to six carbon atoms,cyano, halo and alkylthio having from one to six carbon atoms;

X represents an atom of sulfur or oxygen;

R," represents an alkyl. linear or branched. having one to four carbonatoms, and

R represents an alkyl, linear or branched, having one to four carbonatoms, alkoxy having one to four carbon atoms and possibly substitutedby alkoxy having one to four carbon atoms, or R represents an aminogroup in which R, and R the same or different, represent either hydrogenor an alkyl, linear or branched, having one to three carbon atoms, andmore particularly R represents a member selected from the groupconsisting of alkyl having one to four carbon atoms, alkoxy having oneto four carbon atoms, alkoxyalkoxy having one to four carbon atoms ineach alk, and

where R, and R are members selected from the group consisting ofhydrogen and alkyl having one to three carbon atoms.

The term alkyl used here above designates particularly methyl, ethyl,propyl, isopropyl or n-butyl and the h.2-diethoxythiophosphoryloxy-3-ethylthio-7 ,8-.

ih -py w tLZal-wrim M ne-1 :229-

The compounds of formula I are endowed withpesti- I cidal propertiesparticularly as insecticides and/or acaricides which make them suitableto control noxious organisms and particularly insects and acarids.

The insecticidal properties of these compounds can be demonstratedparticularly by tests on Prodenia lituru, Ceralin's capitata,Aphisfabl'ze, BIateIIa germanica or Musca domestica which are describedlater.

' The process of preparation of the organophosphate ester derivatives offormula I is characterized in that a compound of the formula ll:

wherein A and Y have the above-assigned values. is reacted with ahalogenophosphate of the formula [I]:

(III) such as acetone, acetonitrile, benzene, methanol or ethyl acetate,under, preferably, anhydrous conditions in the presence of a basic agentsuch as an alkali metal carbonate, an alkali metal lower alkanolateand/or a tertiary organic amine base such as triethylamine,trimethylamine or pyridine. The basic agent may also be the alkali metalderivative of the compound of formula II as formed from the reaction ofthe compound of formula ll with an alkali metal lower alkanolate in asolvent such as a lower alkanol.

In the case where Y is hydrogen, R represents an alkyl and'R representsan alkoxy, for compounds of formula I, these compounds can be preparedby reacting a compound of the formula with a trialkyl phosphite.Preferably, this reaction is conducted with an excess of thetrialkylphosphite and for example at temperatures of from 50C to 125C.

The invention also comprises the insecticidal and/or acaricidalcompositions containing, as active material, at least one of thecompounds of formula I. These compositions can be presented in the formof powders, granules, suspensions, emulsions, solutions, containing theactive principle, for example, in mixture with a vehicle and/orananionic, cationic or nonionic surfaceactive agent assuring, amongother things, a uniform dispersion of the substances of the composition.The vehicle utilized can be a liquid such as water, alcohol,hydrocarbons or other organic solvents, mineral, vegetable or animaloil, or a powder such as talc, clays, silicates, Kieselguhr.

The insecticidal liquidsor powders for foliage applications containpreferably from 20 to percent by weight of the active material FormulaI.

The acaricidal liquids or powders for foliage applications containpreferably from 20 percent to 80 percent by weight of the activematerial of formula I.

or several other pesticidal agents is contacted with the insects and/oracarids.

The compounds of formula 11. utilized as starting materials in theprocess of the invention. can be prepared accordingto a processanalogous to that described by Le Berre et a1. Bull. Soc. Chim. 1969,3137.

4-hydroxy-l,6-dihydro-azepino-[1,2-a]-pyrimidine- 6-one was described byGlushkov et a1, Zhur. Obsh- I chei. Khim. 31. 189 (1961).2,3-dihydro-7-hydroxythiaz0lo-[3.2-a1-pyrimidine-5-one was described byDashkevieh. Zhur. Obshchei, Khim. 31, 3723 (1961). Certain compounds offormula II are not described in the literature. These are2-hydroxy-6.7.8,9-tetrahydropyrido-[ l .2-a]-pyrimidine-4-one,2-hydroxy-3- ethylthio-7.8-dihydro-6H-pyrrolo-l1,2-al-pyrimidine- 4-one,1,6-dihydro-4-hydroxy-5-bromo-azepino-l1,2- al-pyrimidine-o-one. andl,6-dihydro4-hydroxy-5- isopropyl-azepino-[l,2-al-pyrimidine-6 one, allof whose preparations are given as exemplary later in the examples.

The compounds of the formula N OH 1 I A N Br can be prepared by theaction ofN-bromo-succinimide on compounds of the formula The followingexamples are illustrative of the practice ol the invention without beingdeemed limitative in any respect.

EXAM PLES Preparation A:

2-h yd roxy-6,7 ,8.9-tetrahydro-pyrido-l 1 .2a 1- pyrimidine-done 6.5 gmofsodium were introduced into 300 cc ofethanol and. after thedisappearance of the sodium. 19 gm of imino-pyridine hydrochloride and22.5 gm of ethyl malonate were added thereto. The reaction mixture washeated to reflux and maintained there for sixteen hours. The insolublesformed were eliminated by filtration. The reaction mixture wasconcentrated to dryness and some water was added thereto. The aqueousmixture was acidified to a pH of 3 by the addition of an aqueoussolution of hydrochloric acid. The precipitate formed was isolated byvacuum filtering and 13.8 gm of 2-hydroxy-6, 7,8,9-tetrahydro-pyrido-[1.2-alpyrimidine-4-one melting at 270C (with decomposition), wasobtained.

1R. Spectra absorption at 1709 and 1606" corresponding to C=O,absorption at 1587"" corresponding to C=C. absorption at 1529"corresponding to C=N.

Preparation B 2-hydroxy3-ethylthio-7.8-dihydro-6H-pyrrolo-[ 1.241]-pyrimidine-4-one 19.5 gm of imino-pyrrolidine and 52 gm ofethylethylthio-malonate were mixed. This mixture was heated to 200C.maintained at this temperature'for fifteen minutes, and then cooled. Theresidue obtained was ground in the presence of ether. The resultingpowder was isolated by vacuum filtering and 31 gm of 2-hydroxy-3-ethylthio-7,8-dihydro-6H-pyrrolo-l l .2-a pyrimidine-4-one wasobtained.

[.R. Spectra absorption at 1720 ""f corresponding to C= O.

absorptions corresponding to C=C. C=N. OH.

Preparation C:

azepino-[1.2-al-pyrimidine-6-one 4-hydroxy-5-bromo- 1 .6-dihydro- 37 gmof 4-hydroxy-1.6-dihydro-azepino-l 1.2-alpyrimidine-6-one was introducedinto 300 cc of methanol. 36.6 gm of N-bromo-succinimide were addedprogressively and then the reaction mixture was agitated for 16 hours atroom temperature. The precipitate formed was isolated by vacuumfiltering. washed and dried. 38 gm of 4-hydroxy-azepino-[1.2-al-pyrimidine- 6-one 5-brom0-l .-dihydro. melting at 265C (with decomposition). was obtained.

1. R. Spectra absorption at 1694 cmfl. 1683cm corresponding to C= O.absorption at 1618 cm corresponding to C C. absorption at l569cmjand1540cm corresponding to C N, absorption corresponding to OH.

Preparation D:

1.6-dhydro-4-hydr0xy-5-isopropyl-azepino-[ 1 .2-a]- pyrimidine-6-one 45gm of sodium ethylate were introduced into 450 cc of ethanol. 63 gm ofethyl isopropyl-malonate and 50 gm of the sulfate ofcaprolactamidinewere added to the solution obtained. The reaction mixture was heated toreflux and maintained there for four hours. The solvent was theneliminated by distillation under reduced pressure. The residue wasdissolved in water and acidified to a ph of 3 with an aqueoushydrochloric acid solution. The precipitate formed was isolated byvacuum filtration and dried. 47 gm of 1,6-dihydro-4-hydroxy-5-isopropyl-azepino-l l,2-a]-pyrimidine-6-one was obtained, which waspurified by dissolution in an aqueous sodium hydroxide solution, thissolution being washed with ethyl acetate and acidified to a pH of 4. Thepurified product had a melting point of 246C. Analysis:

C H N O molecular weight 222.29 1 Calculated:

64.82% C 8.20% H 12.60% N Found:

EX/TMPILE 1 "M v 2-Diethoxytlfiophosfioryloxy g 'v 7 A-dihydro-6H-pyrrolo-[ l ,2-a]-pyrimidine-4-one 36 gm of2-hydroxy-7,8-dihydro-6H-pyrrolo-[l,2-a]- pyrimidine-4-one were placedin suspension in 300 cc of acetone. After homogenization, 28 cc oftriethylamine were added, then 35 cc of 0,0-diethy1 chlorothiophosphatewere introduced drop by drop. The mixture was agitated at roomtemperature for forty-eight hours. Then the precipitate was eliminatedby filtration and the filtrate was evaporated to dryness under reducedpressure. A raw oil was obtained which was subjected to chromatographythrough a column of silica eluting with a chloroform-acetone mixture(1:1). The

Rf 0.5 fraction was evaporated to dryness under reduced pressure. Ayellow oil was obtained which crystallized giving 28 gm of yellowcrystals of 2 diethoxythiophosphoryloxy-7,8-dihydro-6H-pyrrolo-[1,2-a1-pyrimidine-4-one melting at 56 C. Analysis:

C H N O PS; molecular weight 304.307

Calculated:

43.43% C 5.63% H 9.20% N 10.17% P 'Found:

EXAMPLE 2 2-(N -methyl-O-ethyl-thiophosphoramido-oxyi 7 ,8 i

dihydro-6H-pyrrolo-[1,2-a]-pyrimidine-4-one.

35 gm of 2-hydroxy-7,8-dihydro-6H-pyrrolo-[1,2-a]- pyrimidine-4-0ne weremixed with 400 cc of anhydrous acetonitrile, 32 gm of potassiumcarbonate and 50 gm of ethyl N-methyl-thiophosphoramido chloridate. Thereaction mixture was agitated for 16 hours at room temperature and thenthe insolubles were eliminated by vacuum filtration. The filtrate wasevaporated under reduced pressureand 55 gm of a red oil was obtained.This oil was purified by subjecting it to chromatography through acolumn of silica eluting with an acetonechloroform-cyclohexane mixture(1:111). The fraction of Rf 0.3 was separated. The solvents wereeliminated under reduced pressure and 9 gm of Z-(N-methyl-O-ethyl-thiophosphoramido-oxy)-7,8-dihydro-6H-pyrrolo-[l,2-a]-pyrimidine-4-one were obtained, which crystallizedslowly giving yellowish crystals melting at 85C.

weight 289.295

EXAMPLE 3 2-(O-ethylN ,N-dimethyl-thiophosphoramido-oxy)- 7,8-dihydro-6H-pyrrolo-[1,2-a]-pyrimidine-4-one 22 gm of sodium methylate wereintroduced therein. The mixture was maintained under agitation until thetemperature returned to 20C. The precipitate formed was eliminated byfiltration. The filtrate was evaporated to dryness. The residue wastaken up in ether, triturated, and 88 gm of the sodium salt of2-hydroxy- 7,8-dihydro-6H-pyrrolo-[l ,2-a]-pyrimidine-4-one was isolatedby vacuum filtering.

Step B: 2-(o-ethyl NNdimethylthiophosphoramido-oxy)-7,8-dihydro-6H-pyrrolo-[l,2-a]-pyrimidine-4-one 88 gm of a sodium salt of2-hydroxy-7,8-dihydro-6H- pyrrolo-[ l ,2al-pyrimidine-4-one and 63 cc ofethyl N- dimethyl-thiophosphoramido-chloridate were introduced into 700cc of acetonitrile. The mixture was heated to reflux for 33 hours. Theprecipitate formed was eliminated by filtration. The filtrate evaporatedto dryness and gm of red oil was obtained. This oil was subjected tochromatography through silica eluting with acyclohexane-acetone-chloroform mixture (1:1:1) in order to obtain someyellowish crystals which were purified by washing with essence G. 27.5gm of 2-(O-ethyl-N,N-dimethyl-thiophosphoramido-0xy)-7,8-dihydro-6H-pyrrolo-[1,2-a]-pyrimidine-4-one were thus obtainedmelting at 63 C.

Analysis:

C H N O Ps; molecular weight 303.322 Calculated:

43.55% C 5.98% H 13.85% N 10.20% P 10.57% S Found:

EXAMPLE 4 34 gm of 2,3-dihydro-7-hydroxy-thiazolo-[3,2-a]-pyrimidine-S-one and 28 gm of potassium carbonate were introduced into asolution of 35 cc of 0,0-diethyl -chlorothiophosphate in 300 cc ofacetonitrile. The solution thus obtained was heated to reflux for 16hours. The precipitate formed was eliminated by filtration. The filtratewas evaporated to dryness. A red oil was obtained which was subject tochromatography through silica eluting with a cyclohexane-ethyl acetatemixture (2:8). 19 gm of2,3-dihydro-7-(diethoxythiophosphoryloxy)-thiazo1o-[3,2-a]-pyrimidine-5-onewas obtained having a refractive index n,, 1.5711. Analysis:

C H, N O.,PS molecular weight 322.344 Calculated:

37.26% C 4.69% H 8.69% N 9.62% P Found:

EXAMPLE 5 2-Diethoxythiophosphoryloxy-3-bromo-7,8-dihydro- 6H-pyrrolo-[l,2-a]-pyrimidine-4-one 1.1 gm of 2-hydroxy-3-b'romo-7,8-dihydro-6H-pyrrolo-[1,2-a]-pyrimidine-4-one were introduced into a suspensioncontaining 0.8 cc of 0,0-diethyl chlorothiophosphate and 0.7 gm ofpotassium carbonate in 10 cc of acetonitrile. The suspension obtainedwas agi tated for 48 hours. The insolubles were eliminated by E'XAMPLEG2-Diethoxythiophosphoryloxy-3 -methyl-7 ,8-dihydro- 6H-pyrrolo-[l,2-a]-pyrimidine4-one.

Step A: The sodium salt of 2-hydroxy3-methyl- 7 ,8-dihydro-6H-pyrrolo-[1,2-a]-pyrimidine-4-one.

44.5 gm of 2hydroxy-3-methyl-7,8-dihydro-6H-pyrrolo-[l,2-al-pyrimidine-4-one and 14.5 gm of sodium methylate wereintroduced at 40C into 400 cc of methanol. The solution obtained wasagitated for minutes at room temperature and then evaporated to dryness.The crystals obtained were triturated in ether and isolated by vacuumfiltration. 134 gm of the raw sodium salt of2-hydroxy-3-methyl-7,8-dihydro-6H- pyrrolo-[l,2-a]-pyrimidine-4-one werethus obtained.

Step B: 2-Diethoxythiophosphoryloxy-3-methyl- 7,8-dihydro-6H-pyrrolo-[l,2-a]-pyrimidine4-one.

134 gm of the raw salt obtained in Step A were introduced into asolution containing 42.5 cc of 0,0- diethyl chloro-thiophosphate in 500cc of acetonitrile. The mixture was heated to reflux for 36 hours. Theprecipitate formed was eliminated by vacuum filtration and the filtratewas evaporated to dryness. A red oil was obtained which was subject tochromatography through silica eluting with acyclohexa'neacetone-chloroform mixture (1:1:1). A yellow oil of Rf 0.35was obtained which was subject to chromatography again through silicaeluting with a cyclohexaneethyl acetate mixture (3:7). gm of2-diethoxythiophosphoryloxy-3-methyl-7,8-dihydro-6H-pyrrolo-[l,2-a]-pyrimidine-4-one were thus obtained having a refractiveindex 1117 1.5335. Analysis:

C H19N2O PS: molecular weight 318.334 Calculated;

45.28% C 6.02% H 8.80% N 9.73% P Found:

EXAMPLE 7 2,3-Dihydro-8-diethoxythiophosphoryloxy-4H-pyrimido-[2,1-b]-[1,3]-thiazine-6-one (prepared according to the methodof Schobert et al Ann. Chem. 742,91. 1970) 21 gm of potassium carbonateand 28.5 gm of 0,0- diethyl chloro-thio-phosphate were introduced into250 cc of acetonitrile. The mixture was heated to reflux for 3 hours andthen the precipitate formed was eliminated by filtration. The filtratewas evaporated to dryness, then crystallized by the addition of ether.Some yellow crystals were obtained which were subject to chromatographythrough silica with elution with a cyclohexane-chloroform-acetonemixture tlzlzl). 20.! gm of 2.3-dihydro-8-diethoxy-thio- 4 110phosphoryloxy-4H-pyrimido-[2 l -b]-[1 ,3l-thiazine.

6-one were thus obtained melting at 80C.

Analysis: C H N O PS molecular weight 336.37 5 Calculated:

39.29% C 5.09% H 8.33% N 9.20% P Found:

EXAMPLE 8 l,6-Dihydro-4-dimethoxythiophosphoryloxy-azepino-[l,2-a]-pyrimidine-6-one 35 gm of 1,6-dihydro*4-hydroxy-azepino-[l,2-a]pyrimidine-6-one and 27 gm of potassium carbonate were introduced into350 cc of acetonitrile. 32 gm of 0,0-dimethyl chloro-thiophosphate werethen added, and the reaction mixture was agitated for 20 hours at roomtemperature. The mineral salts were eliminated by filtration. Thefiltrate was concentrated to dryness by distillation under reducedpressure. The residue was dissolved in a mixture of cyclohexane andethyl acetate 1:1 The solution obtained was passed through florisil(activated magnesium silicate) and 27 gm of 1,6-dihydro-4-dirnethoxy-thiophosphoryloxy-azepino-[1,2- a]-pyrimidine-6-onewere obtained having a melting point of 99C.

Analysis:

C H N O PS; molecular weight 304.31 Calculated:

43.42% C 5.63% H 9.20% N l0.l8% P Found:

EXAMPLE 9l,6-Dihydro-4diethoxythiophosphoryloxy-azepinoll.2-al-pyrimidine-6-one35 gm of l,6-dihydro-4-hydroxy-azepino-l1.2-111- pyrimidine-6-one and 27gm of potassium carbonate were introduced into 350 cc of acetonitrile.30 cc of .0,0-diethyl chloro-thiophosphate were added thereto. Themixture was agitated for 56 hours at room temperature. The mineral saltswere eliminated by filtration. The filtrate was concentrated to drynessby distillation under reduced pressure. The residue was subject tochromatography through silica gel eluting with a mix- EXAMPLE 101.6-Dihydro-4-dietho xythiophosphoryloxy-S- isopropyl-azepino-[ l,2-a]-pyrimidine-6-one 40 gm of l,6-dihydro-4-hydroxy-5-isopropyl-9291991911 1-Py m ;Qa3liat tpq ssium carbonate and 29 cc of 0,0-diethylchlorothiophosphate were introduced into 400 cc of acetoni trile. Thereaction mixture was heated to reflux and maintained there for 6 hours.Thereafter the mixture was agitated for 60 hours at room temperature.The

was concentrated to dryness by distillation under reduced pressure. Theresidue was purified by chromatography through silica gel eluting with amixture of cyclohexane and ethyl acetate (7:3). 50 gm of 1,6-dihydro-4-diethoxythiophosphoryloxy-S-isopropylazepino-[l,2-a]-pyrimidine-6-onewere obtained having a melting point of 71C. Analysis:

C, H N O PS; molecular weight 374.44 Calculated:

51.33% C 7.27%H 7.48% N 8.27% P Found:

EXAMPLE 112-Dimethoxythiophosphoryloxy-7,8-dihydro-6l'lpyrro1o-[1,2-a]-pyrimidine-4-one 41 gm of 2-hydroxy-7,8-dihydro-6l-1-pyrrole-[1,2-a]-pyrimidine-4-one, 400 mg of topanol, 36.5 gm of potassium carbonate wereintroduced into a mixture of 300 cc of acetone and 30 cc of methanol. 40gm of 0,0- dimethyl chloro-thiophosphate were added thereto. Thereaction mixture was heated to reflux and maintained there for a periodof an hour and 45 minutes. Thereafter, the reaction mixture wasconcentrated to dryness by distillation under reduced pressure. Waterwas added to the residue and the mixture was extracted with ethylacetate. The organic phase was dried and concentrated to dryness bydistillation under reduced pressure. The residue was crystallized fromethyl ether and 23 gm of 2-dimethoxythi0phosphoryloxy-7,8-dihydro-6H-pyrrolo-[1.2-a1-pyrimidine-4-one were obtained having amelting point of 53C.

Analysis:

C H,;,N O,PS; molecular weight 276.25 Calculated:

39.13% C 4.75% H 10.14% N 11.20% P Found:

EXAMPLE-1.2-

2,3-Dihydro-7-dimethoxythiophosphoryloxythiazolo-[3,2-al-pyrimidine--one 12 gm of 2,3-dihydro-7-hydroxy-thiazolo-[3,2-a]-pyrimidine-S-one and 9.8 gm of potassium carbonate were introduced into200 cc of acetonitrile. 8.5 cc of 0,0-dimethy1 chloro-thiophosphate wereintroduced therein. The mixture was agitated for s rnaur'sarreafitemperature. The mineral salts were eliminated by filtration. Thefiltrate was concentrated to dryness by distillation under reducedpressure. The residue was subject to chromatography through silica gelwith elution by a mixture of cyclohexane and ethyl acetate (2:8). 8 gmof2,3-dihydro-7-dimethoxythiophosphoryloxythiazolo-[3,2-a]-5-pyrimidine-5-onewere obtained having a melting point of 84C.

Analysis:

C H N O PS molecular weight 294.29 Calculated:

32.65% C 3.77% H 9.52% N 10.53% P Found:

' mineral salts were eliminated by filtration. The filtrate- EXAMPLE 131,6-Dihydro-4-diethoxyphosphoryloxy-azepino-[1.2- al-pyrim idine-6-one35 gm of 1,6-dihydro-4-hydroxy-azepino-[ l .2-alpyrimidine-6-one wereintroduced into 250 cc of triethyl phosphite. The reaction mixture washeated to C and maintained there for 16 hours. A slight insolubility waseliminated by filtration. The filtrate was concentrated to dryness bydistillation under reduced pressure. The residue was subject tochromatography through silica gel eluting with a mixture of acetone,chloroform and cyclohexane (1:1:1), then subject to chromatographythrough florasil (activated magnesium silicate) eluting with a mixtureof acetone and chloroform 1:1 and concentrated to dryness under reducedpressure. 21 gm of 1.6-dihydro-4-diethoxyphosphoryloxy-azepino-[1,2-a1-pyrimidine- 6-one were obtainedcontaining about 10% of triethyl phosphite having a refractive index n1.4994.

EXAMPLE 14 2-Diethoxythiophosphoryloxy-6,7,8,9-tetrahydropyrido-[1,2-a]-pyrimidine-4-one gel with elution by a mixtureof cyclohexane and ethyl acetate (4:6). 7.96 gm of 2-diethoxythiophosphoryloxy-6.7,8,9-tetrahydro-pyrido-'[l.2-a]-pyrimidine-4-one were obtained having a refractive index of n1.5410. Analysis:

C H N O PS; molecular weight 318.33 Calculated:

45.29% C 6.02% H 8.80% N 9.73% P Found: 45.6 6.2 8.6 9.7

EXAMPLE 15 2-Dimethoxythiophosphoryloxy-6,7,8,9-tetrahydropyrido-[1,2-a]-pyrimidine-4-one 17 gm of2-hydroxy-6,7,8,9-tetrahydropyrido-[1,2- al-pyrimidine-4-one and 24 gmof potassium carbonate were introduced into 200 cc of acetonitrile. 12cc of 0,0-dimethyl chloro-thiophosphate were added thereto. The mixturewas agitated for 1 6 hours at room temperature and next the reactionmixture was heated to 60C and maintained at this temperature for onehour and thirty minutes. The mineral'salts were elimi- EXAMPLE l62-(Methoxy-ethoxy-thiophosphoryloxy)-7,8-dihydro-6H-pyrro|o-[1,2-a]-pyrimidine-4-one 30.4 gm of2-hydroxy-7,8-dihydro-6H-pyrrolo-[1,2-'

a]-pyrimidine-4-one and 27.6 gm of potassium carbonate were introducedinto 300 cc of acetone. This mixture was heated to reflux and maintainedthere for 1 hour, then cooled to 20C. 34.8 gm of O-methyl-O- ethylchlorothiophosphate were added. The reaction mixture was heated to 40Cand maintained at this temperature for 4 hours. The insolubles formedwere eliminated by filtration. The filtrate was concentrated to drynessunder reduced pressure. The residue was subject to chromatographythrough silica gel with elution by a mixture of chloroform and acetone(111-). 6.5 gm of 2-(methoxy-ethoxythiophosphoryloxy)-7,8-dihydro-6H-pyrrolo-[1,2-a]-pyrimidine-4-one were obtained having a melting pointof 71C.

Analysis:

C H N O PS; molecular weight 290.28 Calculated:

41.37% C 5.21% H 9.65% N 10.67% P Found:

EXAMPLE l7 2-(O-ethyl-N-isopropylthiophosphoramido-oxy)-7,8-dihydro-6H-pyrrolo-[1,2-a]-pyrimidine-4-one 30.4 gm of2-hydroxy-7,8-dihydro-6H-pyrrolo-[1,2- al-pyrimidine-4-one and 27.6 gmof potassium carbonate were introduced into 400 cc of acetone. Themixture was agitated for a period of 1 hour at room temperature. Then40.3 gm of ethyl N-isopropyl-thiophos phoramidochloridate was added. Themixture was. agitated for 72 hours at room temperature. The insolublesformed were eliminated by filtration. The filtrate was concentrated todryness by distillation under reduced pressure. The residue was subjectto chromatography through silica gel with elution by a mixture ofacetone, chloroform and cyclohexane (111:1). 17.5 gm of 2-(0-ethyl-N-isopropylthiophosphoramido-oxy)-7,8-clihydro-6H-pyrrolo-[1,2-a]-pyrimidine-4-one were obtained.

Analysis:

C, H N O PS; molecular weight 317.35 Calculated:

45.42% C 6.35% H 13.24% N 9.76% P Found:

EXAMPLE l8 2-[ Ethoxy-( 2-ethoxy -ethoxy-thiophosphoryloxy|7,8-dihydro-6H-pyrrolo-[1,2-a]-pyrimidine-4-one 152 gm of2-hydroxy-7.8-dihydro-6H-pyrrolo-[1,2- aI-pyrimidine-4-one and 13.8 gmof potassium carbonate were introduced into 400 cc of acetone. Themixture was agitated for one hour at room temperature. Then 23.2 gm ofO-ethyl-O-(2-ethoxy-ethyl)chlorothiophosphate were added. The mixturewas agitated for 72 hours at room temperature. The mineral salts wereeliminated by filtration. The filtrate was concentrated to dryness. Theresidue was subject to chromatography through silica gel with elution bya mixture of acetone. chloroform and cyclohexane (1:1:1l). l1.7 gm

of Z-[ethoxy-(Z-ethoxy)-ethoxy-thiophosphoryloxyl1-7,8-dihydro-6H-pyrrolo-[1.2-al pyrimidine-4-one were obtained having arefractive index n 1.5312. Analysis:

- C, H ,N O PS; molecular weight 348.36 Calculated:

44.82% C 6.08% H 8.04% N 8.89% P Found:

EXAMPLE 19 2-( Di-n-propyloxythiophosphoryloxy)-7,8-dihydro-6- 'PY -I 1-a]-pyrimidine-4-on 9.2 gm of 2-hydroxy-7,8-dihydro-6H-pyrrolo-[1.2-al-pyrimidine-4-one and 8.5 gm of potassium carbonate were introducedinto a mixture of cc of acetone and 20 cc of methanol. 13 gm of0,0-di-n-propyl chloro-thiophosphate were added. The reaction mixturewas heated to reflux and maintained there for five hours, and thencooled. The mixture was concentrated to dryness and water was added tothe residue.

The aqueous material was extracted with ether. The ethereal phases weredried and concentrated to dryness. The residue was subject tochromatography through silica gel eluting with a mixture of cyclohexane,acetone and chloroform (1:1:1). 15 gm of2-(di-npropyloxythiophosphoryloxy)-7,8-dihydro-6H-pyrrolo-[l,2-a]-pyrimidine-4-one were obtained having a refractive index n1.5290. Analysis:

C H N O PS; molecular weight 332.36 Calculated:

47.00% C 6.37% H 8.42% N 9.32% P Found: j

EXAMPLE 20 2-Diisopropyloxythiophosphoryloxy-7.8-dihydro-6H- pyrrolo-[l,2-al-pyrimidine-4-one pyrrolo-[l,2-a]-pyrimidine-4-one were obtainedhav-- ing a melting point of 30C. Analysis:

C H N O PS: molecular weight 332.36 Calculated:

46.480/0 C 6.37% H. 8.43% N 9.32% P Found:

- EXAMPLE 21 7 ,8 dihydro 6l l pyrrolo l ,2-a]-pyrimjdine-4-'one 9.2- gmof2 hydroxy 7 ,8-dihydro-6H pyrrolo-[1,2- a]-pyrimidine-4-one and 8.5 gmof potassium carbonate were introduced into a mixture of 150 cc ofacetone and 20 cc of methanol. 15 gm of 0,0-di-n-butylchlorothiophosphate were added. The reaction mixture was heated toreflux, maintained there for 5 hours, then concentrated to dryness.Water was added to the residue and the aqueous phase was extracted withether. The ethereal phase were dried and concentrated to dryness. Theresidue was subject to chromatography through silica gel eluting with amixture of cyclohexane, chloroform and acetone 1:1 :1 11 gm of2-(di-nbutyloxythiophosphoryloxy) 7,8-dihydro-6H-pyrrolo-[l,2-a]-pyrimidine-4-one were obtained having a refractive index n l.5200. Analysis:

C H N O 'PS; 360.40 Calculated:

50.00% C 6.99%H 7.77% N 8.58% P Found:

50.3 6.9 7.6 8.8 were introduced into a mixture of 150 cc of acetone and20 cc of methanol. 15 gm of O,O-di-n-butyl chlorothiophosphate Weredded.

' The reaction mixture was heated to reflux, maintained there for 5hours, then concentrated to dryness. Water was added to the residue andthe aqueous phase was extracted with ether. The ethereal phase weredried and concentrated to dryness. The

residue was subject to chromatography through silica gel eluting with amixture of cyclohexane, chloroform and acetone (l:l:l ll gm of2-(di-nbutyloxythiophosphonyloxy)7,8-dihydro-6H-pyrrolo-[l,2-a]-pyrimedine-4-one were obtained having a refractive indexn 1.5200.

Analysis: CIH1Z5NQO4PS; Calculated:

50.00% C 6.99% H 7.77% N 8.58% P Found:

EXAMPLE 22 2-Diethoxythiophosphoryloxy-3-ethylthio-7,8-dihydro- 31 gm ofZ-hydroxy-3-ethylithio-7,8-dihydro-6H- pyrrolo-ll,2-a]-pyrimidine-4-one,205 gm of potasthiophosphate were introduced into 350 cc of acetonitrile. The mixture was agitated for 60 hours at room EXAMPLE 23Study of the insecticidal properties of 2-diethoxythio designatedhereafter as Compound A.

A. Test on Aphis fabae Some bean plants were utilized which were dividedinto three groups:

a. The first group ofplants was treated by Compound A, 1 ml of solutioncontaining mg of Compound A 5 per liter was sprinkled on each leaf. Eachleaf was infested with 20 plant lice and each leaf was encircled withgauze in order to hinder the departure ofthe plant lice.

b. The second group of plants was treated in the same fashion as thegroup ofplants ofgroup a), but replacing TABLE I Concentration in mg/ 1Activity 0 Product 24 hours i 2 hours 48 hours Compound A 5 0 Dimethoate5 3 .6

f Conclusion: Compound A possesses a very good activity on Aphis a ae.

B. Test on Ceratitis capitata v In this test covered Petri dishes areutilized which are divided into three groups:

a. lnthe dishes of group a), 1 ml of acetonic solution of Compound A wasinserted at concentrations oflOO, 10.7.5; 5, 2.5 and 1 mg of Compound Aper liter.

b. In the dishes of group b), the corresponding solutions of Dimethoatewere utilized in place of those of Compound A.

c. in the dishes of group c), no'solution was inserted and. itwas usedasthe control group.

Twenty .Ceratitis capitataflies aged three days were placed in eachPetri dish of group a), b) and c)-, and the lids were placed thereon.The living insects and those 'killed by Compound A and Dimethoate atdifferent intervals of time were counted. The activity of compound andthat of Dimethoate are expressed as a percentage of the reduction of thenumber of living insects. The results are given in Table II below:

TABLE ll Activity Concentration Product in mg/] 1 hour 24 hoursDimethoate .5 5

Conclusion: Compound A has a very good activity on Cerariris capirala.

C. Test on Prodenia litura (caterpillars) Salad leaves which were brokeninto bits of 8 mm in diameter were utilized. Each piece of leaf wasplaced in a box at a ratio of one piece of leaf per box, and the boxeswere divided into three groups:

milk or water. The controls were effected one hour,

and then 24 hours after the treatment. The experimen- TABLE V a. Thepieces of salad leaves of the boxes in group a) were treated with theCompound A at an amount of 4 1000RPM 2500 ppm 500 ppm p.14of aqueoussolution ofCompound A on each piece, and with solutions containing5,000, 2,500, 1,250 and 3 38 33 9 625 mg of Compound A per liter. 4

b. Operating in the same manner for group b), but 10 Compound A wasreplaced by Carbaryl (or l-N- 0 Test on Aphl-s fabae p y N' y This testwas effected by contact-ingestion on beans. Nothmg was Placed on thebits of left g p After pulverization of the solution of the product 7 Ineach box of groups i caterpillar was tested, the infestation rate ofindividual aphids per inserted. The caterpillars remaining alive andthose l t of b ns was made. The bean plants were killed by the twoinsecticides at different intervals of wrapped in gauze in order tohinder the departure of time were counted. The activity of Compound Aand the plant lice. A counting of living and dead insects as that ofCarbaryl are expressed as a percentage of the a function of time wasmade. The results are expressed reduction of the number of livingcaterpillars. The re- 20 in a percentage of Abbott efficacy (taking intoaccount sults are given in Table III below. the controlled test).

' TABLE n Concen- Amount of active Activity Prodtration product absorbeduct in mg/l in pg 1 hour 24 hours 48 hours 5000 20 100 100 100 2500 i0100 r00 r00 Com- 1250 5 90 I00 I00 pound A 625 2.5 80 I00 I00 5000 20100 I00 100 2500 I0 100 100 100 Cttr- 1250 5 100 100 100 harylConclusion: Compound A possesses a very good activity on Pmdenia lilura,superior to that of carbaryl.

7 EXAMPLE 24 The resuhs obtained are given in Table VI below:

Study of the insecticidal activity of x2-dimethoxythio-phosphoryloxy-7,8-dihydro-6H- pyrrolo-[l,2-a]-pyrimidine-4-one 100 ppm ppm A. Test on Blatella germanica: Ihour 60 0 This test was. effected by micro-contact. Larvae of 24 hours()0 39 the cockroaches chosen according to their length re- 48 hours 100l 00 ceived a micro-drop of an acetonic solution of the th econd andthird air product to be tested between e S t. n p D. Test on Prodemalztura of legs. After the treatment, the test insects were o This testwas effected on the caterpillars of Prodenia held in semi-darkness at 20C, and were nourished. The

t l m de 24 hours 48 hours and then 5 d3 5 htura. It IS a test byingestion. An acetonrc solution of a S g t X riniemal reslms ex ressed i50 the product to be tested was deposited on bits of salad l. ..l i.llll .p;l-.. 39.2? leaves of 8 mm in diameter which were disposed in aPercentage of mortallty are g'ven m a e e closed plastic boxes of 5 cmin diameter. Fifteen caterpillars were utilized per treatment(caterpillars aged 10 TABLE IV days in average). The caterpillars wereheld at 20C and 50% relative humidity, and were fed. The controls 5,000ppm. 1.250 p.p.m. 625 ppm. were effected 1 hour, 24 hours and 48 hoursafter treat- 90 75 ment. The experimental results obtained expressed as24 h I00 i 48 mo 95 35 a percentage of mortality are given in Table VI]below.

5 days 100 100 90 B. Test on Musca domestica TABLE Vll This test waseffected by micro-contact. The flies received a micro-drop of acetonicsolution of the product 500 p.p.m. 250 ppm. 125 ppm. 62.5 being testedon the dorsal thorax, after having been put P-P- to sleep with ether.The insects were maintained at [ham 0 0 0 0 O I 24 h 100 so so 20 C and50% relative humidity. They were fed with 48 mo 00 I00 E. Test on larvaeofdomestic flies (Musca domestica) This test was effected bycontact-ingestion. It consists of depositing 2 ml of an acetonicsolution of the compound to be tested on 1 gm of bran, placed in a watchglass. The solvent was allowed to evaporate. Then the treated bran wasdeposited in a plastic box. Two ml of milk was added and after havingbeen mixed the material was contaminated with larvae of domestic fliesaged 3 to 4'days. There were 3 tests by concentration. The larvae weremaintained at 20C and 50% relative humidity. The controls were effected48 hours and 8 days after the treatment. The experimental resultsobtained expressed as a percentage of mortality are given in Table Vlllbelow:

TABLE Vlll 5,60 dp.p. rn. 500 ppm.

48 hours 37 28 8 days 97 87 Conclusion:

i (out). j

wherein n represents an integer from 2 to 3,

Y represents a member selected from the group consisting of hydrogen,alkyl having one to six carbon atoms, halo and alkylthio having one tosix carbon atoms,

X represents a member selected from the group consisting of sulfur andoxygen,

R, represents an alkyl having one to four carbon atoms,

R represents a member selected from the group consisting of alkoxyhaving one to four carbons atoms, alkoxyalkoxy having one to four carbonatoms alkoxyalkoxy having one to four carbon atoms in each alk, and

aI-pyrimidine-S-one.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION patent 3. 857 ,838Dated December 31, 1-974 Inventor) Jacques Perronnet et al Page 1 of 2It is certified that error appears in the above-identified patent andthat said Letters Patent are hereby corrected as shown below:

' Column 5, line 4 omitted in 11,2 a]

Column 5 line 4 and 5 "pyrrdo-A-pyrimidone" should have been omitted.

Column 6 lines 41 and 42 "4zhydrojcy-wazepinofll ,2a] myrimidine- 6-one5.bromo-.l,6edihydro" should read we 4ehydroxy-5 bromo-l,6- dihydroazepino-ILZ-a]pyrimidine 6one Column 8, line 5-8, insert Step A: Thesodium salt of 2- hydroxy-J,8-dihydro+6H+pyrroloIl,Z a]-pyrimidine4-one.60 gm of 2hydroxy-7',8-dihydro6H pyrrolo-[1,Z a]-pyrimidine-4- one wereintroduced into 400 cc on methanol. Next Column 9, line 3, insert withan ethyl acetatecyclohexane mixture (9:1) 406 mg after the word"eluting" Column 9, line 56, Before "pyrimido" insert 24.6 gm of 2,Zmdihy-dro 8-hydroxy4H= Column 13, line 68, (111211)" should be (121:1)

Column 14, line 60, "0/0" should he Column 14, line 66, Before "7',8-dihyd-ro"' insert e- 2- (Di:nebutyloxwthiophophorloxy)e Column 15, lines19 38 all material after "50 .3 6 .9 7.6 8 8" should be cancelled asduplicate of lines l-l9 Column 15, line. 58, "c" in formula should be CUNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patmm No.3,857,838 Datai December 31 1974 Invmworhfl Jacques Perronnet et al.Page 2 f 2 It is certified that error appears in the above-identifiedpatent and that said Letters Patent are hereby corrected as shown below:

Column 17, line 7, the "4" in after ,ul should be omitted.

Column 19, line 24, "testz" should be tests Signed and Scaled thisseventeenth Day Of February 1976 [SEAL] Attest:

C. MARSHALL DANN A I testing Officer (or

1. AN ORGANO PHOSPHATE ESTER HAVING THE FORMULA
 2. An organophosphateester of claim 1 wherein Y'' is hydrogen.
 3. An organophosphate ester ofclaim 1 being2,3-dihydro-8-diethoxythiophosphoryloxy-4H-pyrimido-(2,1-b)-(1,3)-thiazine-6-one.4. An organophosphate ester of claim 1 being2,3-dihydro-7-dimethoxythiophosphoryloxy-thiazolo-(3,2-a)-pyrimidine-5-one.